Semin Neurol 2013; 33(02): 157-166
DOI: 10.1055/s-0033-1348959
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

End-of-Life and Brain Death in Acute Coma and Disorders of Consciousness

David M. Greer
1   Department of Neurology, Yale University School of Medicine, New Haven, Connecticut
,
Gioacchino G. Curiale
1   Department of Neurology, Yale University School of Medicine, New Haven, Connecticut
› Author Affiliations
Further Information

Publication History

Publication Date:
25 July 2013 (online)

Abstract

Consulting neurologists are often asked to evaluate patients in acute nontraumatic coma. The authors review prognostication of functional outcomes, determining brain death, and managing end-of-life care. Prognostication of outcome after cardiac arrest in comatose patients is a frequently encountered scenario with high-stakes implications. However, current guidelines are limited by a failure to address the use of therapeutic hypothermia and thus may lead to overly pessimistic outcome prediction. Pupillary light responses and corneal reflexes remain highly predictive clinical signs of a poor prognosis. Motor responses have a high false-positive rate for predicting a poor outcome, especially in patients treated with therapeutic hypothermia. Ancillary testing with electroencephalography, somatosensory evoked potentials, serum neuron-specific enolase, and neuroimaging is often useful in predicting outcomes. Brain death is a clinical condition of irreversible coma of known cause with absent brainstem reflexes and apnea. An understanding of the value of confirmatory testing and the potential for confounding factors is essential in making a correct diagnosis. As coma carries a high mortality rate, neurologists must be capable of guiding goals of care, discussing end-of-life issues, and understanding organ-procurement procedures.

 
  • References

  • 1 Levy DE, Caronna JJ, Singer BH, Lapinski RH, Frydman H, Plum F. Predicting outcome from hypoxic-ischemic coma. JAMA 1985; 253 (10) 1420-1426
  • 2 Zandbergen EGJ, Hijdra A, Koelman JH , et al; PROPAC Study Group. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology 2006; 66 (1) 62-68
  • 3 Fischer C, Luauté J, Adeleine P, Morlet D. Predictive value of sensory and cognitive evoked potentials for awakening from coma. Neurology 2004; 63 (4) 669-673
  • 4 Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S. Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006; 67 (2) 203-210
  • 5 Posner JB, Plum F. Plum and Posner's diagnosis of stupor and coma. 4th ed. New York, NY: Oxford University Press; 2007
  • 6 Roger VL, Go AS, Lloyd-Jones DM , et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics—2011 Update: A Report from the American Heart Association. Circulation 2011; 123 (4) e18-e209
  • 7 Nichol G, Thomas E, Callaway CW , et al; Resuscitation Outcomes Consortium Investigators. Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA 2008; 300 (12) 1423-1431
  • 8 Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002; 346 (8) 549-556
  • 9 Bernard SA, Gray TW, Buist MD , et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346 (8) 557-563
  • 10 Deakin CD, Morrison LJ, Morley PT , et al; Advanced Life Support Chapter Collaborators. Part 8: Advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation 2010; 81 (1) (Suppl. 01) e93-e174
  • 11 Peberdy MA, Callaway CW, Neumar RW , et al. Part 9: Post-Cardiac Arrest Care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122 (18) (Suppl. 03) S768-S786
  • 12 Bouwes A, Binnekade JM, Kuiper MA , et al. Prognosis of coma after therapeutic hypothermia: a prospective cohort study. Ann Neurol 2012; 71 (2) 206-212
  • 13 Al Thenayan E, Savard M, Sharpe M, Norton L, Young B. Predictors of poor neurologic outcome after induced mild hypothermia following cardiac arrest. Neurology 2008; 71 (19) 1535-1537
  • 14 Blondin NA, Greer DM. Neurologic prognosis in cardiac arrest patients treated with therapeutic hypothermia. Neurologist 2011; 17 (5) 241-248
  • 15 Sunde K, Dunlop O, Rostrup M, Sandberg M, Sjøholm H, Jacobsen D. Determination of prognosis after cardiac arrest may be more difficult after introduction of therapeutic hypothermia. Resuscitation 2006; 69 (1) 29-32
  • 16 Fugate JE, Wijdicks EF, Mandrekar J , et al. Predictors of neurologic outcome in hypothermia after cardiac arrest. Ann Neurol 2010; 68 (6) 907-914
  • 17 Mokhtarani M, Mahgoub AN, Morioka N , et al. Buspirone and meperidine synergistically reduce the shivering threshold. Anesth Analg 2001; 93 (5) 1233-1239
  • 18 Fukuoka N, Aibiki M, Tsukamoto T, Seki K, Morita S. Biphasic concentration change during continuous midazolam administration in brain-injured patients undergoing therapeutic moderate hypothermia. Resuscitation 2004; 60 (2) 225-230
  • 19 Tortorici MA, Kochanek PM, Poloyac SM. Effects of hypothermia on drug disposition, metabolism, and response: a focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system. Crit Care Med 2007; 35 (9) 2196-2204
  • 20 Samaniego EA, Mlynash M, Caulfield AF, Eyngorn I, Wijman CA. Sedation confounds outcome prediction in cardiac arrest survivors treated with hypothermia. Neurocrit Care 2011; 15 (1) 113-119
  • 21 Rossetti AO, Oddo M, Logroscino G, Kaplan PW. Prognostication after cardiac arrest and hypothermia: a prospective study. Ann Neurol 2010; 67 (3) 301-307
  • 22 Greer DM, Yang J, Scripko PD , et al. Clinical examination for outcome prediction in nontraumatic coma. Crit Care Med 2012; 40 (4) 1150-1156
  • 23 Jørgensen EO, Holm S. The natural course of neurological recovery following cardiopulmonary resuscitation. Resuscitation 1998; 36 (2) 111-122
  • 24 Rundgren M, Rosén I, Friberg H. Amplitude-integrated EEG (aEEG) predicts outcome after cardiac arrest and induced hypothermia. Intensive Care Med 2006; 32 (6) 836-842
  • 25 Krumholz A, Stern BJ, Weiss HD. Outcome from coma after cardiopulmonary resuscitation: relation to seizures and myoclonus. Neurology 1988; 38 (3) 401-405
  • 26 Arnoldus EP, Lammers GJ. Postanoxic coma: good recovery despite myoclonus status. Ann Neurol 1995; 38 (4) 697-698
  • 27 Morris HR, Howard RS, Brown P. Early myoclonic status and outcome after cardiorespiratory arrest. J Neurol Neurosurg Psychiatry 1998; 64 (2) 267-268
  • 28 Rossetti AO, Oddo M, Liaudet L, Kaplan PW. Predictors of awakening from postanoxic status epilepticus after therapeutic hypothermia. Neurology 2009; 72 (8) 744-749
  • 29 Gendo A, Kramer L, Häfner M , et al. Time-dependency of sensory evoked potentials in comatose cardiac arrest survivors. Intensive Care Med 2001; 27 (8) 1305-1311
  • 30 Bouwes A, Binnekade JM, Zandstra DF , et al. Somatosensory evoked potentials during mild hypothermia after cardiopulmonary resuscitation. Neurology 2009; 73 (18) 1457-1461
  • 31 Leithner C, Ploner CJ, Hasper D, Storm C. Does hypothermia influence the predictive value of bilateral absent N20 after cardiac arrest?. Neurology 2010; 74 (12) 965-969
  • 32 Schoerkhuber W, Kittler H, Sterz F , et al. Time course of serum neuron-specific enolase. A predictor of neurological outcome in patients resuscitated from cardiac arrest. Stroke 1999; 30 (8) 1598-1603
  • 33 Daubin C, Quentin C, Allouche S , et al. Serum neuron-specific enolase as predictor of outcome in comatose cardiac-arrest survivors: a prospective cohort study. BMC Cardiovasc Disord 2011; 11: 48
  • 34 Torbey MT, Selim M, Knorr J, Bigelow C, Recht L. Quantitative analysis of the loss of distinction between gray and white matter in comatose patients after cardiac arrest. Stroke 2000; 31 (9) 2163-2167
  • 35 Choi SP, Park HK, Park KN , et al. The density ratio of grey to white matter on computed tomography as an early predictor of vegetative state or death after cardiac arrest. Emerg Med J 2008; 25 (10) 666-669
  • 36 Wu O, Batista LM, Lima FO, Vangel MG, Furie KL, Greer DM. Predicting clinical outcome in comatose cardiac arrest patients using early noncontrast computed tomography. Stroke 2011; 42 (4) 985-992
  • 37 Wu O, Sorensen AG, Benner T, Singhal AB, Furie KL, Greer DM. Comatose patients with cardiac arrest: predicting clinical outcome with diffusion-weighted MR imaging. Radiology 2009; 252 (1) 173-181
  • 38 Greer D, Scripko P, Bartscher J , et al. Serial MRI changes in comatose cardiac arrest patients. Neurocrit Care 2011; 14 (1) 61-67
  • 39 Greer DM. MRI in anoxic brain injury. Neurocrit Care 2004; 1 (2) 213-215
  • 40 Guidelines for the determination of death. Report of the medical consultants on the diagnosis of death to the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. JAMA 1981; 246 (19) 2184-2186
  • 41 Wijdicks EF. Determining brain death in adults. Neurology 1995; 45 (5) 1003-1011
  • 42 Greer DM, Varelas PN, Haque S, Wijdicks EF. Variability of brain death determination guidelines in leading US neurologic institutions. Neurology 2008; 70 (4) 284-289
  • 43 Wijdicks EF, Varelas PN, Gronseth GS, Greer DM. American Academy of Neurology. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2010; 74 (23) 1911-1918
  • 44 Bradac GB, Simon RS. Angiography in brain death. Neuroradiology 1974; 7 (1) 25-28
  • 45 American Clinical Neurophysiology Society. Guideline 3: minimum technical standards for EEG recording in suspected cerebral death. J Clin Neurophysiol 2006; 23 (2) 97-104
  • 46 Wieler H, Marohl K, Kaiser KP, Klawki P, Frössler H. Tc-99m HMPAO cerebral scintigraphy. A reliable, noninvasive method for determination of brain death. Clin Nucl Med 1993; 18 (2) 104-109
  • 47 Bonetti MG, Ciritella P, Valle G, Perrone E. 99mTc HM-PAO brain perfusion SPECT in brain death. Neuroradiology 1995; 37 (5) 365-369
  • 48 Wijdicks EF. The case against confirmatory tests for determining brain death in adults. Neurology 2010; 75 (1) 77-83
  • 49 Döşemeci L, Cengiz M, Yilmaz M, Ramazanoĝlu A. Frequency of spinal reflex movements in brain-dead patients. Transplant Proc 2004; 36 (1) 17-19
  • 50 Ivan LP. Spinal reflexes in cerebral death. Neurology 1973; 23 (6) 650-652
  • 51 Beckmann YY, Ciftçi Y, Seçil Y, Eren S. Fasciculations in brain death. Crit Care Med 2010; 38 (12) 2377-2378
  • 52 Saposnik G, Maurino J, Saizar R, Bueri JA. Spontaneous and reflex movements in 107 patients with brain death. Am J Med 2005; 118 (3) 311-314
  • 53 Ropper AH. Unusual spontaneous movements in brain-dead patients. Neurology 1984; 34 (8) 1089-1092
  • 54 Kagawa-Singer M, Blackhall LJ. Negotiating cross-cultural issues at the end of life: “You got to go where he lives.”. JAMA 2001; 286 (23) 2993-3001
  • 55 Frost DW, Cook DJ, Heyland DK, Fowler RA. Patient and healthcare professional factors influencing end-of-life decision-making during critical illness: a systematic review. Crit Care Med 2011; 39 (5) 1174-1189
  • 56 Emanuel EJ. A review of the ethical and legal aspects of terminating medical care. Am J Med 1988; 84 (2) 291-301
  • 57 Paris JJ, Reardon FE. Court responses to withholding or withdrawing artificial nutrition and fluids. JAMA 1985; 253 (15) 2243-2245
  • 58 Weil MH, Wiel CJ. How to respond to family demands for futile life support and cardiopulmonary resuscitation. Crit Care Med 2000; 28 (9) 3339-3340
  • 59 Singer PA, Martin DK, Kelner M. Quality end-of-life care: patients' perspectives. JAMA 1999; 281 (2) 163-168
  • 60 Emanuel LL, Barry MJ, Stoeckle JD, Ettelson LM, Emanuel EJ. Advance directives for medical care—a case for greater use. N Engl J Med 1991; 324 (13) 889-895
  • 61 Pope TM. Legal fundamentals of surrogate decision making. Chest 2012; 141 (4) 1074-1081
  • 62 Lang F, Quill T. Making decisions with families at the end of life. Am Fam Physician 2004; 70 (4) 719-723
  • 63 Heyland DK, Frank C, Groll D , et al. Understanding cardiopulmonary resuscitation decision making: perspectives of seriously ill hospitalized patients and family members. Chest 2006; 130 (2) 419-428
  • 64 Curtis JR, Patrick DL, Shannon SE, Treece PD, Engelberg RA, Rubenfeld GD. The family conference as a focus to improve communication about end-of-life care in the intensive care unit: opportunities for improvement. Crit Care Med 2001; 29 (2, Suppl): N26-N33
  • 65 Stapleton RD, Engelberg RA, Wenrich MD, Goss CH, Curtis JR. Clinician statements and family satisfaction with family conferences in the intensive care unit. Crit Care Med 2006; 34 (6) 1679-1685
  • 66 McDonagh JR, Elliott TB, Engelberg RA , et al. Family satisfaction with family conferences about end-of-life care in the intensive care unit: increased proportion of family speech is associated with increased satisfaction. Crit Care Med 2004; 32 (7) 1484-1488
  • 67 Davidson JE, Powers K, Hedayat KM , et al; American College of Critical Care Medicine Task Force 2004-2005, Society of Critical Care Medicine. Clinical practice guidelines for support of the family in the patient-centered intensive care unit: American College of Critical Care Medicine Task Force 2004-2005. Crit Care Med 2007; 35 (2) 605-622
  • 68 Balaban RB. A physician's guide to talking about end-of-life care. J Gen Intern Med 2000; 15 (3) 195-200
  • 69 Lee Char SJ, Evans LR, Malvar GL, White DB. A randomized trial of two methods to disclose prognosis to surrogate decision makers in intensive care units. Am J Respir Crit Care Med 2010; 182 (7) 905-909
  • 70 Peberdy MA, Ornato JP, Larkin GL , et al; National Registry of Cardiopulmonary Resuscitation Investigators. Survival from in-hospital cardiac arrest during nights and weekends. JAMA 2008; 299 (7) 785-792
  • 71 Gehlbach TG, Shinkunas LA, Forman-Hoffman VL, Thomas KW, Schmidt GA, Kaldjian LC. Code status orders and goals of care in the medical ICU. Chest 2011; 139 (4) 802-809
  • 72 Holloway RG, Quill TE. Treatment decisions after brain injury—tensions among quality, preference, and cost. N Engl J Med 2010; 362 (19) 1757-1759
  • 73 Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. A definition of irreversible coma. JAMA 1968; 205 (6) 337-340
  • 74 Truog RD, Miller FG. The dead donor rule and organ transplantation. N Engl J Med 2008; 359 (7) 674-675
  • 75 Verheijde JL, Rady MY, McGregor JL. Brain death, states of impaired consciousness, and physician-assisted death for end-of-life organ donation and transplantation. Med Health Care Philos 2009; 12 (4) 409-421
  • 76 Truog RD. Consent for organ donation—balancing conflicting ethical obligations. N Engl J Med 2008; 358 (12) 1209-1211
  • 77 Williams MA, Lipsett PA, Rushton CH , et al; Council on Scientific Affairs, American Medical Association. The physician's role in discussing organ donation with families. Crit Care Med 2003; 31 (5) 1568-1573
  • 78 Wood KE, Becker BN, McCartney JG, D'Alessandro AM, Coursin DB. Care of the potential organ donor. N Engl J Med 2004; 351 (26) 2730-2739